This study compared the effectiveness of doxycycline and bleomycin in the treatment of cystic hygroma and it was found that both were equally effective. Fever and redness were noticed in fewer patients with Doxycycline whereas pain and skin pigmentation were noticed in respectively 6 and 2 patients treated with Doxycycline. There were no significant differences with regards to age, sex, weight, location of anomaly, and pretreatment between these two groups. However, a slight male predominance was found in the current study, which is consistent with other studies [6,7,8,9]. In the current study, in both groups, half of the lesions were found in the posterior triangle of the neck which is similar to other reports. Hygromas usually reside in close proximity to large veins and lymphatic ducts, in the neck (75%), axilla (20%), and others (5%) such as mediastinum, retroperitoneum, pelvis, and groin [10]. Rawat et al. found 57.9% of lesions were in the neck region [8].
Bleomycin acts by two ways first through cytotoxic effect and second by sclerosis. It is a DNA synthesis inhibitor and its exact mechanism of action in cystic hygroma is not known; however, it is believed that it may produce a non-specific inflammatory process that results in the fibrosis of the cysts. Intralesional Bleomycin microsphere in oil emulsion has been reported to have a good response as it is retained for a long period of time. Pulmonary fibrosis is associated with treatment with a high dosage of bleomycin. The safe upper limit for the dosage of bleomycin in a single session is 30 mg/m2. In most published studies, where small doses of bleomycin were used, there was no pulmonary fibrosis in any of their patients [4]. Nonetheless, bleomycin is expensive and is not easily available in many countries.
Doxycycline is an inexpensive and easily available antibiotic. The exact mechanism by which doxycycline is effective as a sclerosant is unknown, but an inflammatory process that results in fibrosis and involution of cysts is speculated [14]. It also functions as an angiogenesis inhibitor by interfering with cell proliferation and migration via inhibition of matrix metalloproteinase (MMP) and suppression of vascular endothelial growth factor (VEGF)-induced angiogenesis and lymphangiogenesis [6]. The injectable form of doxycycline is also readily available with compounding capability and requires reconstitution in a normal saline solution at a concentration of 10 mg/ml. In addition, doxycycline theoretically may prevent infectious complications. Doxycycline has an established safety profile. Adverse effects associated with doxycycline are reported as local erythema, edema at the injection site, and pain [7, 14]. Mild swelling occurs following injection and typically improves after 24–48 h [6]. Burrow et al. reported that doxycycline caused severe discomfort on injection, requiring general anesthesia in most patients. Pain requiring narcotic analgesia is common for 1 to 3 h post procedure [6]. In this study, the procedure was performed on outpatient basis with local anesthesia (Injection 2% lignocaine) after taking consent from the parent. Local anesthesia was given as patient’s guardian did not give consent for general anesthesia and in other study procedures were done by local anesthesia [11].
Doxycycline showed excellent response in 86.7% of participants in contrast to 60% with Bleomycin in this study. Several studies evaluated the efficacy of sclerotherapy with doxycycline for the treatment of macrocystic lymphatic malformations. They reported that 85–93% of patients had excellent to moderate responses with doxycycline [6, 7, 12, 14]. There was no patient with a poor response in this study which is similar to some other studies [6, 7, 14]. Here excellent response means response category >90%, good response means response category 60–90%, fair 25–50%, and poor <25 %[6]. Rawat and Saxena found 42–57% complete resolution of cystic hygroma treated with intralesional bleomycin, which is also similar to our study [8, 13]. Partial response with bleomycin was in 33% in this study, which was similar with Saxena and Hajela (36%). However, but Saxena and Hajela noted 22% with no response after repeated injection of bleomycin for 4 times, while in this study, no response was found in 6.7% of patients which was later treated by surgery. Saddal also reported that 6% of patients had no response in his study [15].
Adverse effects of doxycycline and bleomycin were compared in the current study. In group A, one third of the respondents (33.3%) had fever and redness whereas in broup B, the majority of the respondents (43%) had fever and 33% of respondents had redness. Moreover, doxycycline was found very cost-effective as the overall cost of doxycycline was almost 20 taka (0.25 UD$) in 4 weeks of treatment whereas the overall cost of bleomycin in four sessions was 125 US$. Bleomycin is also rarely available in our market nowadays. For these reasons, doxycycline may be considered as a safe, effective, and cheaper alternative for bleomycin in the treatment of cystic hygroma in low- and middle-income countries.